Department of Pharmaceutics, Shenyang Pharmaceutical University, Liaoning Province, Shenyang, PR China.
ACS Appl Mater Interfaces. 2013 Jan;5(1):103-13. doi: 10.1021/am302246s. Epub 2012 Dec 24.
A novel spherical nanosilica matrix (SNM) together with chitosan (CTS) encapsulated SNM (CTS-SNM) was developed in order to investigate the feasibility of using chitosan to regulate drug release rate from porous silica and obtain an oral sustained drug delivery system. To achieve this goal, we synthesized a spherical nanosilica matrix (SNM) and incorporated chitosan chains on the SNM surface. Solvent evaporation method was adopted to load the model drug carvedilol into SNM and CTS-SNM. The physicochemical properties of the drug carriers and drug-loaded composites were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The structural changes in CTS-SNM in simulated gastrointestinal fluid as well as the relationships between swelling effect of chitosan and in vitro drug release behaviors were investigated. Pharmacokinetic and bioavailability aspects were also discussed. The results showed that the powerful dispersing effect of SNM and the blocking action due to the swelling of chitosan were the two main factors contributing to the sustained drug release behavior. The swelling effect of chitosan in an acidic environment together with the shrinking effect in a relatively alkaline environment allowed regulation of drug release behavior in simulated gastrointestinal fluid. An in vivo study showed that the bioavailability of CAR was improved 182% compared with that of the commercial capsule when SNM was used as the drug carrier. As for CAR-CTS-SNM, the T(max) of CAR was delayed by about 3.4 h and the bioavailability was slightly increased in comparison with the commercial capsule. We believe that SNM and CTS-SNM developed in this study will help increase the use of polymers and inorganic materials in pharmaceutical applications and stimulate the design of oral drug delivery systems for immediate or sustained release of poorly water-soluble drugs.
为了研究壳聚糖（CTS）调节多孔硅药物释放速率的可能性，获得口服缓控释给药系统，我们开发了一种新型球形纳米硅基质（SNM）与壳聚糖（CTS）包封 SNM（CTS-SNM）。为实现这一目标，我们合成了球形纳米硅基质（SNM），并在 SNM 表面结合了壳聚糖链。采用溶剂蒸发法将模型药物卡维地洛载入 SNM 和 CTS-SNM。通过扫描电子显微镜（SEM）、透射电子显微镜（TEM）、氮气吸附、X 射线衍射（XRD）、差示扫描量热法（DSC）和热重分析（TGA）系统研究了药物载体和载药复合材料的理化性质。考察了 CTS-SNM 在模拟胃肠道液中的结构变化以及壳聚糖溶胀效果与体外药物释放行为之间的关系。还讨论了药代动力学和生物利用度方面的问题。结果表明，SNM 的强大分散效果和壳聚糖溶胀引起的阻断作用是导致药物持续释放行为的两个主要因素。壳聚糖在酸性环境中的溶胀作用和在相对碱性环境中的收缩作用允许调节模拟胃肠道液中的药物释放行为。体内研究表明，与使用商业胶囊相比，当 SNM 用作药物载体时，CAR 的生物利用度提高了 182%。对于 CAR-CTS-SNM，CAR 的 T（max）延迟了约 3.4 小时，与商业胶囊相比，生物利用度略有提高。我们相信，本研究开发的 SNM 和 CTS-SNM 将有助于增加聚合物和无机材料在药物应用中的使用，并刺激设计用于立即或持续释放难溶性药物的口服药物传递系统。
